What not to do with active pharmaceutical ingredient (API) batch records? Tear them out of a company logbook ahead of an FDA inspection, for one. Earlier this month, Indian drugmaker Indiana Chem-Port learned that lesson the hard way.
The FDA has dinged Indiana Chem-Port with a laundry list of problems related to controls, cleaning, maintenance, testing and quality assurance in its API production operation. The regulator handed down a five-observation warning letter earlier this month after inspecting Indiana Chem-Port’s Gujarat, India, manufacturing facility in August last year.
The company dropped the ball when it came to making sure equipment surfaces in contact with APIs didn’t alter the quality of the drug ingredients, the FDA said. The company also failed to ensure equipment used to make drug ingredients was “suitable for its intended use” and correctly maintained.
FDA investigators pointed to “rust-like residues” on product contact surfaces of equipment labeled as clean. Indiana Chem-Port also used tape on certain paddles to “prevent black material from screws from contaminating [their] API,” the FDA said in its partially redacted warning.
Further, Indiana Chem-Port failed to show that its manufacturing process could consistently reproduce API to necessary quality standards. The company also failed to validate multiple manufacturing processes and “made several changes to [its] manufacturing process without justification or change control,” the FDA said in its letter.
The company didn’t properly validate written procedures for equipment cleaning and maintenance, either. What’s more, the company lacks “assurance that [its] equipment is adequately cleaned to prevent cross-contamination from other products,” the regulator added.
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On the testing front, Indiana Chem-Port came up short on design of a documented, ongoing stability testing program, which is necessary to monitor the stability of drug ingredients, the FDA said. Results from those tests help confirm appropriate storage conditions, plus retest or expiration dates, the agency added.
Investigators cited a particular batch of API, manufactured in 2016, which was stored in a reserve sample room that was “not controlled for humidity.”
“Despite basing your retest dating on this batch, you destroyed batch records associated with the [redacted batch],” the FDA continued.
Finally, Indiana Chem-Port lacks a quality unit “independent” from its production team, which fulfills quality assurance and quality control duties, the FDA said.
Meanwhile, the regulator also observed “numerous” signed and partially-completed batch records missing a “controlled copy” stamp. Further, the company destroyed an API batch record for a certain drug ingredient lot, despite the fact that it’s still in distribution in the U.S.
Given the nature of Indiana Chem-Port’s violations, the FDA has recommended the company enlist a manufacturing consultant. The company is on the hook to rectify its cleanliness, maintenance, testing and control troubles, the FDA said.
Recently, Indian manufacturing compatriot Aurobindo Pharma got into hot water with the FDA over its own API operation. That warning letter chastised the drugmaker for failing to adequately investigate batch failures of drug ingredients, among other concerns.
Aurobindo has faced similar violations in the past, with the FDA alleging in its letter that “repeated failures demonstrated that executive management oversight and control over the manufacture of drugs is inadequate.”
